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CN102665681A - Composition of dexibuprofen transdermal hydrogel - Google Patents

Composition of dexibuprofen transdermal hydrogel Download PDF

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Publication number
CN102665681A
CN102665681A CN2010800577381A CN201080057738A CN102665681A CN 102665681 A CN102665681 A CN 102665681A CN 2010800577381 A CN2010800577381 A CN 2010800577381A CN 201080057738 A CN201080057738 A CN 201080057738A CN 102665681 A CN102665681 A CN 102665681A
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China
Prior art keywords
dexibuprofen
hydrogel
alcohol property
sodium
transdermal hydrogel
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CN2010800577381A
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Chinese (zh)
Inventor
斯图尔杰弗里特·伯格曼
桑帕斯库马尔·德佛拉简
塞沃库马尔·拉玛林格穆
安娜森蒂尔威尔·帕拉尼萨米
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Shasun Pharmaceuticals Ltd
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Shasun Pharmaceuticals Ltd
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Publication of CN102665681A publication Critical patent/CN102665681A/en
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof

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  • Dermatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pain & Pain Management (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Rheumatology (AREA)
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Abstract

Stable non-alcoholic transdermal hydrogel of dexibuprofen was prepared by using a simple manufacturing process, and the experimental trials showed that the pH modifying agent, antioxidant and water miscible solvent are the essential excipients to obtain stable non-alcoholic transdermal hydrogel of dexibuprofen. The dexibuprofen hydrogel prepared using carbopol as a gelling polymer produced an opaque gel, whereas hydrogel prepared using hyroxypropyl methylcellulose (HPMC) as a gelling polymer produced a transparent gel. There was no significant changes observed with respect to physical description, pH, assay and particularly to the related substance values when the hydrogels were subjected to the stability study at accelerated condition (40 DEG C / 75% RH) for 3 months in laminated tubes.

Description

The novel composition of dexibuprofen transdermal hydrogel
Technical field
The present invention relates to a kind of topical pharmaceutical's compositions and its preparation method that contains dexibuprofen (dexibuprofen) ［ (S)-2-(4-isobutyl phenenyl) propanoic acid ］.
Background technology
Therefore ibuprofen (2-(4-isobutyl phenenyl) propanoic acid) has a chiral centre, has two kinds of enantiomers, i.e. S (+)-ibuprofen (dexibuprofen) and R (-)-ibuprofen are also referred to as (S+)-ibuprofen and (R-)-ibuprofen.The racemic form of being made up of equivalent S (+)-ibuprofen and R (-)-ibuprofen is exclusively used in the current available commercial formulation; And also use the water soluble salt of ibuprofen in these commercial formulation, for example lysinate (lysinate), arginine salt (arginate), sodium salt, potassium salt etc.The raceme ibuprofen has relative high melt point (about 78 ℃), and two kinds of stereoisomer S (+)-ibuprofen of ibuprofen and R (-)-ibuprofen are 52 ℃ to 54 ℃ following fusions.The dissolubility of all multi-form ibuprofen in water is all relatively poor.It should be noted that as if independent S (+) form produce antiphlogistic activity, and R (-) form does not produce (S. Adam people such as (S.Adams), contemporary medical science research viewpoint (Curr.Med.Res.Opin.) 3,552 (1975); S. Adam people such as (S.Adams), pharmacology pharmacodynamic magazine (J.Pharm.Pharmaco.), 28,256-257 (1976)).
United States Patent (USP) discloses the water alcohol property gel composite of (S)-ibuprofen for No. 5093133, and it is the effective mediator that transmits (S+)-ibuprofen via the skin percutaneous.In this patent, (S+)-the water alcohol property gel of ibuprofen is pure through using with preparation: the 40-60% that gets off; The non-volatile solvent of 0-20%; The 2.0-5.0% gellant; The adjusting pH value is 3.5 to 6.0 enough alkali; And water.
United States Patent (USP) discloses the medical composition that is emulsifiable paste, foams (foam) or club (stick) form No. 5767161; It contains 2.5-10 weight % (S)-2-(4-isobutyl phenenyl) propanoic acid, 20-30 weight % ethanol and 5-50 weight % propylene glycol, and the ratio of ethanol and propylene glycol is 0.6-1 to 4:1.This patent also reports with respect to contain the dermal osmosis that the known topical pharmaceutical compositions of equivalent or more amount ibuprofen is reached, and the dermal osmosis of this active component increases.
United States Patent (USP) discloses the local composite of the novel biphase liquid that transmits S (+)-ibuprofen for No. 6368618, it is characterized in that Transdermal absorption and effect strengthen.In this patent, binary system is made up of water and oil phase, and oil phase contains S (+)-ibuprofen of relative higher concentration, makes it can directly be used for being dispensed to horny layer, and does not have the rate limit diffusion process that begins from the inertia oil phase in the conventional emulsifiable paste.
United States Patent (USP) discloses the medical composition that is used for per os, rectum or topical administration No. 5696165, and it contains (S)-ibuprofen sodium salt as active component.Have the advantage that is superior to S (+) 2-(4-isobutyl phenenyl) propionate aspect the medical composition of this patent report S (-) 2-(4-isobutyl phenenyl) sodium propionate and extra prescription moisture in preparation, advantage is that S (-) 2-(4-isobutyl phenenyl) sodium propionate will resist by the excipient that contains hydroxyl (for example monohydric alcohol, dihydroxylic alcohols, trihydroxylic alcohol or polyhydric alcohol) esterification.
Such as in the prior art announcement, dexibuprofen is to use a large amount of alcohol or uses binary system to be deployed into local composite to strengthen Transdermal absorption and effect.
Therefore, the local composite that continues to need allotment simple manufacturing approach preparation capable of using and should also provide the dexibuprofen of effective transdermal penetration.
Summary of the invention
Target of the present invention
A target of the present invention is the non-alcohol property transdermal hydrogel of preparation dexibuprofen.
Another target of the present invention is the non-alcohol property transdermal of the clear hydrogel of preparation dexibuprofen.
Content of the present invention
The present invention relates to a kind of local medical composition that contains dexibuprofen that uses, more particularly relate to a kind of non-alcohol property dexibuprofen transdermal hydrogel and its preparation method.The non-alcohol property transdermal hydrogel of stablizing of dexibuprofen is to prepare through the use simple manufacturing method, and experimentation shows that pH regulator agent, antioxidant and water-miscible solvent are the essential excipient of stablizing non-alcohol property transdermal hydrogel that obtains dexibuprofen.Use carbopol (carbopol) to produce opaque gel, and use hydroxypropyl emthylcellulose (HPMC) to produce transparent gel as the prepared hydrogel of gel polymer as the prepared dexibuprofen hydrogel of gel polymer.When in laminated tube acceleration environment (40 ℃/when hydrogel being carried out stability study and keeping 3 months under 75%RH), in physical behavior, pH value, analysis with especially do not observe significant change aspect the related substances value.
Description of drawings
Do not have
The specific embodiment
The present invention relates to a kind of local medical composition that contains dexibuprofen that uses, more particularly relate to a kind of non-alcohol property transdermal hydrogel and its preparation method of dexibuprofen.
Local NSAID preparation is usually used in treating pain and the inflammation relevant with joint and muscle.Three major advantages that local NSAID is superior to the per os treatment of pain relevant with joint and muscle and inflammation are:
I) NSAID of higher concentration is delivered to the position of wanting;
Ii) only the NSAID of 1-3% has been reduced the probability of gastrointestinal upset or ulcer by systemic absorption; With
Iii) low blood level reduces the incidence rate of drug interaction.
The ibuprofen topical formulations can be used for treating pain and the inflammation relevant with joint and muscle.Therefore ibuprofen (2-(4-isobutyl phenenyl) propanoic acid) has a chiral centre, has two kinds of enantiomers, i.e. S (+)-ibuprofen (dexibuprofen) and R (-)-ibuprofen are also referred to as (S)-ibuprofen and (R)-ibuprofen.It should be noted that as if independent S (+) form produce antiphlogistic activity, and R (-) form does not produce (S. Adam people such as (S.Adams), contemporary medical science research viewpoint (Curr.Med.Res.Opin.) 3,552 (1975); S. Adam people such as (S.Adams), pharmacology pharmacodynamic magazine (J.Pharm.Pharmaco.), 28,256-257 (1976)).
Local NSAID preparation commonly used comprises emulsifiable paste, ointment and gel, and current partial water gel is just welcome day by day because of its cooling effect and non-greasy character.
In the prior art, dexibuprofen is to use a large amount of alcohol or uses binary system and be deployed into the topical gel composite to strengthen Transdermal absorption and effect.
The present invention relates to a kind of local medical composition that contains dexibuprofen that uses, more particularly relate to the non-alcohol property transdermal hydrogel and its preparation method of dexibuprofen.
According to the present invention, the method for the non-alcohol property transdermal hydrogel of preparation dexibuprofen comprises following steps:
Step (i) is scattered in gel polymer in the pure water and makes its soaked overnight,
Step (ii) is dissolved in antiseptic in the pure water, then dexibuprofen is scattered in wherein,
Step (iii), (menthol) is dissolved in the triethanolamine with menthol,
Step (iv), under continuous stirring, blend step (iii) with step (ii),
Step (v), is mixed propylene glycol and PEG 400; This mixture is added in the diethylene glycol monoethyl ether (transcutol-P), then adds Essential lavender oil (lavender oil) and fully mixing,
Step (vi), with step (v) add to step (iv) in and fully mix and
Step (vii), under constant agitation, (is vi) added step in the step (i) to obtain even gel at last.
According to the present invention, in fact the non-alcohol property transdermal hydrogel of dexibuprofen can be transparent translucent or opaque.
Except that the active component dexibuprofen, the present invention also comprises one or more and is selected from the pharmaceutically acceptable excipient that comprises following group: gellant, pH regulator agent, spreadability regulator, water-miscible solvent, smoothing preparation, antiseptic, antioxidant, surfactant, chelating agen, penetration enhancer, defoamer and flavoring agent etc.
According to the present invention, the optional self-contained following group of one or more gellant: carbomer (carbomer), hydroxypropyl emthylcellulose (HPMC), hydroxyethyl-cellulose (HEC), poloxamer (poloxamer), hydroxypropyl cellulose (HPC), methylcellulose (MC), collagen protein, gelatin, agar, alginic acid and its sodium salt (for example sodium alginate), carrageenan (carrageenan) and its sodium salt or potassium salt, tragacanth, pectin, guar gum (guar gum), xanthan gum, gellan gum (gellan gum), polyacrylamide, polyvinyl alcohol, polyethylene and its copolymer etc.
According to the present invention, the optional self-contained following group of one or more pH regulator agent: sodium hydroxide, citric acid, sodium citrate, triethanolamine, diethanolamine etc.
According to the present invention, the optional self-contained following group of one or more smoothing preparations: menthol, thymol (thymol), Camphora etc.
According to the present invention, the optional self-contained following group of one or more antiseptic: the sodium salt of methyl parahydroxybenzoate (methyl paraben), propyl p-hydroxybenzoate (propyl paraben), other antiseptic (like salicylic acid and its salt), chlorhexidine hydrochloride (chlorhexidine hydrochloride), phenoxyethanol, sodium benzoate, methyl parahydroxybenzoate (methyl para-hydroxybenzoate), ethylparaben (ethyl para-hydroxybenzoate), propyl p-hydroxybenzoate (propyl para-hydroxybenzoate), butyl p-hydroxybenzoate (butyl para-hydroxybenzoate) etc.
According to the present invention; The optional self-contained following group of at least a oil-soluble and/or water soluble antioxidant: Yoshinox BHT (BHT), ascorbyl palmitate, butylated hydroxy anisole (BHA) (BHA), PA, quinhydrones, n-propyl gallate, remove first dihydro guaiaretic acid (nordihydroguiaretic acid), ascorbic acid, Sodium Benzoate, sodium pyrosulfite, sodium hydrogensulfite, sodium thiosulfite, sodium formaldehyde sulphoxylate, arabo-ascorbic acid, thioglycerol, sulfo-sorbierite, thiocarbamide, thioglycollic acid, cysteine hydrochloride, 1; 4-two nitrine dicyclos-(2; 2,2)-octane etc.
According to the present invention, one or more surfactants selected from the following groups: alkyl sulfate (e.g. sodium lauryl sulfate and sodium myristyl sulfate), N-acyl sarcosinate (e.g., N - Sodium lauroyl sarcosinate and sodium N-myristoyl sarcosinate), sodium dodecylbenzenesulfonate, hydrogenation coconut fatty acid monoglyceride sulfate, sodium lauryl sulfoacetate, N-acyl glutamic salts (e.g., N-palmitoyl glutamate), N-methyl-acyl taurine salt, N-methyl-acyl alanine salt, α-olefin sulfonate, sodium dioctyl sulfosuccinate Sodium; N-alkyl group of glycerol (such as N-lauryl diaminoethyl glycerol and N-myristyl diaminoethyl glycerol), N-alkyl-N-carboxymethyl ammonium betaine 2 - alkyl -l - sodium hydroxyethyl imidazolinium betaine; polyoxyethylene alkyl ethers, polyoxyethylene alkyl aryl ethers, polyoxyethylene lanolin alcohols, polyoxyethylene glycerol mono-fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene fatty acid esters, higher fatty acid glycerides, sorbitan fatty acid esters, Park Dubrovnik type (pluronic? type) surfactants and polyoxyethylene sorbitan fatty acid esters (such as polyoxyethylene sorbitan monooleate and polyoxyethylene sorbitan monolaurate) and so on.
According to the present invention, the optional self-contained following group of one or more spreadability regulators: Polyethylene Glycol, propylene glycol, glycerol, light liquid paraffin etc.
According to the present invention, the optional self-contained following group of one or more water-miscible solvents: Polyethylene Glycol, propylene glycol, glycerol etc.Water-miscible solvent (being cosolvent) will exist, with help the lytic activity agent, other must excipient.
According to the present invention; The optional group below self-contained of one or more penetration enhancers: sad and its derivant, polyoxy glyceride and its derivant, triglyceride and its derivant, lauric acid and its derivant, oleic acid and its derivant, diethylene glycol monoethyl ether (diethylene glycol monoethyl ether, Transcutol-P) etc.
According to the present invention, the optional self-contained following group of one or more chelating agen: ethylenediaminetetraacetic acid (EDTA), EDTA sodium, EDTA disodium, citric acid, tartaric acid etc.
According to the present invention, the optional self-contained following group of one or more defoamer: Simethicone (simethicone), simethicone (dimethicone) etc.
According to the present invention, the optional self-contained following group of one or more flavoring agents: Essential lavender oil, Oleum Rosae Rugosae, menthol, anethole, carvone, eugenol, limonene, ocimene (ocimene), Decanol, citronellol, α-terpinol, methyl salicylate, methyl acetate, geraniol acetate, cineole, linalool, ethyl linalool, vanillin, thymol, Oleum Menthae Rotundifoliae, Oleum menthae, Fructus Citri Limoniae oil, orange oil, sage oil (sage oil), oil of rosemary, Oleum Cinnamomi, allspice oil, Cortex Cinnamomi leaf oil, wintergreen oil, Oleum Caryophylli, Folium eucalypti globueli (Eucalyptus globulus Labill.) wet goods.
Instance:
Following instance is illustrative, but does not certainly limit the scope of the invention.
Instance-1 (table-1) is through using carbopol as the non-alcohol property transdermal of the prepared dexibuprofen of gel polymer hydrogel:
Numbering Composition Weight %
1. Dexibuprofen 10.00
2. Carbopol 971P 2.50
3. Diethylene glycol monoethyl ether 3.30
4. Triethanolamine 7.20
5. Propylene glycol 1.00
6. PEG400 1.00
7. Menthol 0.05
8. Sodium pyrosulfite 0.20
9. Sodium benzoate 0.20
10. Essential lavender oil 0.05
11. Pure water Supply 100
Amount to 100.00
The fabrication schedule of instance 1:
1. under agitation, carbopol 971P is scattered in the pure water, continues 15 minutes, and make its soaked overnight.
2. sodium pyrosulfite and sodium benzoate are dissolved in the pure water, then dexibuprofen are scattered in wherein.
3. menthol is dissolved in the triethanolamine.
4. under constant agitation, step 3 is added in the step 2, obtain settled solution.
5. mix propylene glycol and PEG 400, this mixture is added in the diethylene glycol monoethyl ether, then add Essential lavender oil and fully mixing.
6. step 5 is added in the step 4 and fully and mix.
7. last, under constant agitation, step 6 is added in the step 1, obtain even gel.
Instance-2 (table-2) is through using HPMC as the non-alcohol property transdermal of the prepared dexibuprofen of gel polymer hydrogel:
Numbering Composition Weight %
1. Dexibuprofen 10.0
2. HPMC?K4M 2.5
3. HPMC?E5 0.3
4. Lutrol?F68 5.0
5. Diethylene glycol monoethyl ether 3.3
6. Propylene glycol 1.0
7. PEG400 3.0
8. Menthol 0.1
9. Sodium pyrosulfite 0.2
10. Sodium benzoate 0.2
11. Triethanolamine 7.2
12. Simethicone 0.00016
13. Essential lavender oil 0.1
14. Pure water Supply 100
Amount to 100.0
The fabrication schedule of instance 2:
1. under agitation, HPMC K4M, HPMC E5, Lutrol F68 are scattered in the pure water, continue 15 minutes, and make its soaked overnight.
2. Simethicone is added in the step 1 and fully and mix.
3. sodium pyrosulfite and sodium benzoate are dissolved in the water, then dexibuprofen are scattered in wherein.
4. menthol is dissolved in the triethanolamine.
5. under constant agitation, step 4 is added in the step 3, obtain settled solution.
6. mix propylene glycol, PEG 400, this mixture is added in the diethylene glycol monoethyl ether, then add Essential lavender oil and fully mixing.
7. step 6 is added in the step 5.
8. under constant agitation, step 7 is added in the step 2, obtain even gel.
Instance-3 (table-3) is through using carbopol as the non-alcohol property transdermal of the prepared dexibuprofen of gel polymer hydrogel:
Numbering Composition Weight %
1. Dexibuprofen 5.00
2. Carbopol 971P 2.50
3. Diethylene glycol monoethyl ether 3.30
4. Triethanolamine 7.20
5. Propylene glycol 1.00
6. PEG400 1.00
7. Menthol 0.05
8. Sodium pyrosulfite 0.20
9. Sodium benzoate 0.20
10. Essential lavender oil 0.05
11. Pure water Supply 100
Amount to 100.00
The fabrication schedule of instance 3:
1. under agitation, carbopol 971P is scattered in the pure water, continues 15 minutes, and make its soaked overnight.
2. sodium pyrosulfite and sodium benzoate are dissolved in the pure water, then dexibuprofen are scattered in wherein.
3. menthol is dissolved in the triethanolamine.
4. under constant agitation, step 3 is added in the step 2, obtain settled solution.
5. mix propylene glycol and PEG 400, this mixture is added in the diethylene glycol monoethyl ether, then add Essential lavender oil and fully mixing.
6. step 5 is added in the step 4 and fully and mix.
7. last, under constant agitation, step 6 is added in the step 1, obtain even gel.
Instance-4 (table-4) is through using HPMC as the non-alcohol property transdermal of the prepared dexibuprofen of gel polymer hydrogel:
Numbering Composition Weight %
1. Dexibuprofen 5.0
2. HPMC?K4M 2.5
3. HPMC?E5 0.3
4. Lutrol?F68 5.0
5. Diethylene glycol monoethyl ether 3.3
6. Propylene glycol 1.0
7. PEG400 3.0
8. Menthol 0.1
9. Sodium pyrosulfite 0.2
10. Sodium benzoate 0.2
11. Triethanolamine 7.2
12. Simethicone 0.00016
13. Essential lavender oil 0.1
14. Pure water Supply 100
Amount to 100.0
The fabrication schedule of instance 4:
1. under agitation, HPMC K4M, HPMC E5, Lutrol F68 are scattered in the pure water, continue 15 minutes, and make its soaked overnight.
2. Simethicone is added in the step 1 and fully and mix.
3. sodium pyrosulfite and sodium benzoate are dissolved in the water, then dexibuprofen are scattered in wherein.
4. menthol is dissolved in the triethanolamine.
5. under constant agitation, step 4 is added in the step 3, obtain settled solution.
6. mix propylene glycol, PEG 400, this mixture is added in the diethylene glycol monoethyl ether, then add Essential lavender oil and fully mixing.
7. step 6 is added in the step 5.
8. under constant agitation, step 7 is added in the step 2, obtain even gel.
Experimentation shows that pH regulator agent, antioxidant and water-miscible solvent are the essential excipient of stablizing non-alcohol property transdermal hydrogel that obtains dexibuprofen.Use carbopol to produce opaque gel according to instance 1 and 3, and use HPMC to produce transparent gel as the prepared hydrogel of gel polymer according to instance 2 and 4 as the prepared hydrogel of gel polymer.In addition, in laminated tube, under 40 ℃/75%RH, the hydrogel according to instance 1,2,3 and 4 preparations is carried out stability study and kept 3 months, and physical behavior, pH value, assay value and related substances do not have significant change.
Table 5: the stability data of the non-alcohol property transdermal of the dexibuprofen hydrogel that under 40 ℃/75%RH, prepares according to instance 1,2,3 and 4 is following:
Figure BDA00001779987800091

Claims (9)

1. the non-alcohol property transdermal hydrogel of a dexibuprofen.
2. the transparent transdermal hydrogel of the non-alcohol property of a dexibuprofen.
3. the non-alcohol property transdermal hydrogel of a dexibuprofen, it comprises one or more pH regulator agent, antioxidant and water-miscible solvent basically.
4. according to the non-alcohol property transdermal hydrogel of the described dexibuprofen of arbitrary claim in the aforementioned claim, it comprises one or more surfactants, defoamer, chelating agen, gel polymer, antiseptic, penetration enhancer, smoothing preparation and flavoring agent in addition.
5. the non-alcohol property transdermal hydrogel of dexibuprofen according to claim 4, the wherein optional group below self-contained of one or more gellant: carbomer (carbomer), hydroxypropyl emthylcellulose (HPMC), hydroxyethyl-cellulose (HEC), hydroxypropyl cellulose (HPC), methylcellulose (MC), poloxamer (poloxamer), sodium alginate, carrageenan (carrageenan), tragacanth, pectin, guar gum (guar gum), xanthan gum, gellan gum (gellan gum) and polyacrylamide.
6. the non-alcohol property transdermal hydrogel of dexibuprofen according to claim 3, the wherein optional group below self-contained of one or more water-miscible solvents: Polyethylene Glycol, propylene glycol and glycerol.
7. the non-alcohol property transdermal hydrogel of dexibuprofen according to claim 3, the wherein optional group below self-contained of one or more pH regulator agent: sodium hydroxide, citric acid, sodium citrate, triethanolamine and diethanolamine.
8. the non-alcohol property transdermal hydrogel of dexibuprofen according to claim 3, the wherein optional group below self-contained of one or more antioxidants: sodium benzoate, sodium pyrosulfite, Yoshinox BHT (BHT) and butylatedhydroxyanisole (BHA).
9. according to the non-alcohol property transdermal hydrogel of the described dexibuprofen of arbitrary claim in the aforementioned claim, in fact it can be transparent translucent or opaque.
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